6B0N

Crystal structure of the cleavage-independent prefusion HIV Env glycoprotein trimer of the clade A BG505 isolate (NFL construct) in complex with Fabs PGT122 and PGV19 at 3.39 A

Summary for 6B0N

• Entry DOI: 10.2210/pdb6b0n/pdb
• Related: 6AVN
• Descriptor: PGV19 Fab heavy chain, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (17 entities in total)
• Functional Keywords: viral protein, hiv, envelope, glycoprotein, prefusion trimer, glycan, hiv-1 gp120, hiv-1 gp41, flexible linker, cd4 binding site, vrc01-class lambda antibody, n332 supersite, immune system, neutralizing antibodies, complex, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 180256.35

Authors

Sarkar, A.,Irimia, A.,Wilson, I.A. (deposition date: 2017-09-14, release date: 2018-05-30, Last modification date: 2024-11-06)

Primary citation

Sarkar, A.,Bale, S.,Behrens, A.J.,Kumar, S.,Sharma, S.K.,de Val, N.,Pallesen, J.,Irimia, A.,Diwanji, D.C.,Stanfield, R.L.,Ward, A.B.,Crispin, M.,Wyatt, R.T.,Wilson, I.A.
Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer.
Nat Commun, 9:1956-1956, 2018

PubMed Abstract: Furin cleavage of the HIV envelope glycoprotein is an essential step for cell entry that enables formation of well-folded, native-like glycosylated trimers, releases constraints on the fusion peptide, and limits enzymatic processing of the N-glycan shield. Here, we show that a cleavage-independent, stabilized, soluble Env trimer mimic (BG505 NFL.664) exhibits a "closed-form", native-like, prefusion conformation akin to furin-cleaved Env trimers. The crystal structure of BG505 NFL.664 at 3.39 Å resolution with two potent bNAbs also identifies the full epitopes of PGV19 and PGT122 that target the receptor binding site and N332 supersite, respectively. Quantitative site-specific analysis of the glycan shield reveals that native-like glycan processing is maintained despite furin-independent maturation in the secretory pathway. Thus, cleavage-independent NFL Env trimers exhibit quaternary protein and carbohydrate structures similar to the native viral spike that further validate their potential as vaccine immunogen candidates.

PubMed: 29769533
DOI: 10.1038/s41467-018-04272-y

Experimental method

X-RAY DIFFRACTION (3.4 Å)